MOG-IgG in NMO and related disorders: A multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome

Sven Jarius, Klemens Ruprecht, Ingo Kleiter, Nadja Borisow, Nasrin Asgari, Kalliopi Pitarokoili, Florence Pache, Oliver Stich, Lena Alexandra Beume, Martin W. Hümmert, Marius Ringelstein, Corinna Trebst, Alexander Winkelmann, Alexander Schwarz, Mathias Buttmann, Hanna Zimmermann, Joseph Kuchling, Diego Franciotta, Marco Capobianco, Eberhard SiebertCarsten Lukas, Mirjam Korporal-Kuhnke, Jürgen Haas, Kai Fechner, Alexander U. Brandt, Kathrin Schanda, Orhan Aktas, Friedemann Paul, Markus Reindl, Brigitte Wildemann, in cooperation with the Neuromyelitis Optica Study Group (NEMOS)

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Abstract

Background: A subset of patients with neuromyelitis optica spectrum disorders (NMOSD) has been shown to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). Objective: To describe the epidemiological, clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological features of a large cohort of MOG-IgG-positive patients with optic neuritis (ON) and/or myelitis (n=50) as well as attack and long-term treatment outcomes. Methods: Retrospective multicenter study. Results: The sex ratio was 1:2.8 (m:f). Median age at onset was 31years (range 6-70). The disease followed a multiphasic course in 80% (median time-to-first-relapse 5months; annualized relapse rate 0.92) and resulted in significant disability in 40% (mean follow-up 75±46.5months), with severe visual impairment or functional blindness (36%) and markedly impaired ambulation due to paresis or ataxia (25%) as the most common long-term sequelae. Functional blindess in one or both eyes was noted during at least one ON attack in around 70%. Perioptic enhancement was present in several patients. Besides acute tetra-/paraparesis, dysesthesia and pain were common in acute myelitis (70%). Longitudinally extensive spinal cord lesions were frequent, but short lesions occurred at least once in 44%. Fourty-one percent had a history of simultaneous ON and myelitis. Clinical or radiological involvement of the brain, brainstem, or cerebellum was present in 50%; extra-opticospinal symptoms included intractable nausea and vomiting and respiratory insufficiency (fatal in one). CSF pleocytosis (partly neutrophilic) was present in 70%, oligoclonal bands in only 13%, and blood-CSF-barrier dysfunction in 32%. Intravenous methylprednisolone (IVMP) and long-term immunosuppression were often effective; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal. Full recovery was achieved by plasma exchange in some cases, including after IVMP failure. Breakthrough attacks under azathioprine were linked to the drug-specific latency period and a lack of cotreatment with oral steroids. Methotrexate was effective in 5/6 patients. Interferon-beta was associated with ongoing or increasing disease activity. Rituximab and ofatumumab were effective in some patients. However, treatment with rituximab was followed by early relapses in several cases; end-of-dose relapses occurred 9-12 months after the first infusion. Coexisting autoimmunity was rare (9%). Wingerchuk's 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald criteria for multiple sclerosis (MS) were met by 28%, 32%, 15%, 33%, respectively; MS had been suspected in 36%. Disease onset or relapses were preceded by infection, vaccination, or pregnancy/delivery in several cases. Conclusion: Our findings from a predominantly Caucasian cohort strongly argue against the concept of MOG-IgG denoting a mild and usually monophasic variant of NMOSD. The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis.

Original languageEnglish
Article number280
JournalJournal of Neuroinflammation
Volume13
Issue number1
DOIs
Publication statusPublished - Sep 27 2016

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Keywords

  • Aquaporin-4 antibodies (AQP4-IgG, NMO-IgG)
  • Autoantibodies
  • Azathioprine
  • Barkhof criteria
  • Cerebrospinal fluid
  • Electrophysiology
  • Evoked potentials
  • Glatiramer acetate
  • Infections
  • Interferon beta
  • International consensus diagnostic criteria for neuromyelitis optica spectrum disorders
  • IPND criteria
  • Longitudinally extensive transverse myelitis
  • Magnetic resonance imaging
  • McDonald criteria
  • Methotrexate
  • Multiple sclerosis
  • Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG)
  • Natalizumab
  • Neuromyelitis optica spectrum disorders (NMOSD)
  • Ofatumumab
  • Oligoclonal bands
  • Optic neuritis
  • Outcome
  • Pregnancy
  • Rituximab
  • Therapy
  • Transverse myelitis
  • Treatment
  • Vaccination
  • Wingerchuk criteria 2006 and 2015

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Jarius, S., Ruprecht, K., Kleiter, I., Borisow, N., Asgari, N., Pitarokoili, K., Pache, F., Stich, O., Beume, L. A., Hümmert, M. W., Ringelstein, M., Trebst, C., Winkelmann, A., Schwarz, A., Buttmann, M., Zimmermann, H., Kuchling, J., Franciotta, D., Capobianco, M., ... in cooperation with the Neuromyelitis Optica Study Group (NEMOS) (2016). MOG-IgG in NMO and related disorders: A multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. Journal of Neuroinflammation, 13(1), [280]. https://doi.org/10.1186/s12974-016-0718-0